CD19 CAR-expressing iPSC-derived NK cells effectively enhance migration and cytotoxicity into glioblastoma by targeting to the pericytes in tumor microenvironment

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 174, P. 116436 - 116436

Published: March 19, 2024

In cancer immunotherapy, chimeric antigen receptors (CARs) targeting specific antigens have become a powerful tool for cell-based therapy. CAR-natural killer (NK) cells offer selective anticancer lysis with reduced off-tumor toxicity compared to CAR-T cells, which is beneficial in the heterogeneous milieu of solid tumors. tumor microenvironment (TME) glioblastoma (GBM), pericytes not only support growth but also contribute immune evasion, underscoring their potential as therapeutic targets GBM treatment. Given this context, our study aimed target TME, special focus on expressing CD19, evaluate effectiveness CD19 CAR-iNK against GBM. We performed CAR transduction induced pluripotent stem cell-derived NK (iNK) cells. To determine whether TME GBM, we developed GBM-blood vessel assembloids (GBVA) by fusing spheroids blood organoids. When co-cultured GBVA, migrated towards surrounding Using microfluidic chip, demonstrated cells' targeted action and cytotoxic effects perfusion-like environment. GBVA xenografts recapitulated including human CD19-positive pericytes, thereby enabling application an vivo model validating efficacy Compared spheroids, presence significantly enhanced cell migration proliferation. These results underline within suggesting value

Language: Английский

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Advances of 3D Cell Co-Culture Technology Based on Microfluidic Chips

Biosensors, Journal Year: 2024, Volume and Issue: 14(7), P. 336 - 336

Published: July 10, 2024

Cell co-culture technology aims to study the communication mechanism between cells and better reveal interactions regulatory mechanisms involved in processes such as cell growth, differentiation, apoptosis, other cellular activities. This is achieved by simulating complex organismic environment. Such studies are of great significance for understanding physiological pathological multicellular organisms. As an emerging cultivation technology, 3D based on microfluidic chips, can efficiently, rapidly, accurately achieve co-culture. accomplished leveraging unique microchannel structures flow characteristics chips. The simulate native microenvironment providing a new technical platform studying intercellular communication. It has been widely used research oncology, immunology, neuroscience, fields. In this review, we summarize provide insights into design systems detection methods employed systems, applications these models.

Language: Английский

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Crosstalk and communication of cancer-associated fibroblasts with natural killer and dendritic cells: New frontiers and unveiled opportunities for cancer immunotherapy

Cancer Treatment Reviews, Journal Year: 2024, Volume and Issue: 131, P. 102843 - 102843

Published: Oct. 15, 2024

Language: Английский

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Neuroscience in peripheral cancers: tumors hijacking nerves and neuroimmune crosstalk

MedComm, Journal Year: 2024, Volume and Issue: 5(11)

Published: Oct. 31, 2024

Abstract Cancer neuroscience is an emerging field that investigates the intricate relationship between nervous system and cancer, gaining increasing recognition for its importance. The central governs development of directly affects brain tumors, peripheral (PNS) shapes tumor microenvironment (TME) tumors. Both systems are crucial in cancer initiation progression, with recent studies revealing a more role PNS within TME. Tumors not only invade nerves but also persuade them through remodeling to further promote malignancy, creating bidirectional interaction cancers. Notably, immune cells contribute this communication, forming triangular influences protumor inflammation effectiveness immunotherapy. This review delves into mechanisms connecting focusing on how various cell types influence nerve‒tumor interactions, emphasizing clinical relevance nerve‒immune dynamics. By deepening our understanding interplay nerves, cells, has potential reshape biology insights, inspire innovative therapies, improve outcomes patients.

Language: Английский

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Current status of locally advanced rectal cancer therapy and future prospects

Critical Reviews in Oncology/Hematology, Journal Year: 2023, Volume and Issue: 186, P. 103992 - 103992

Published: April 12, 2023

Language: Английский

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Extracellular matrix stiffness activates mechanosensitive signals but limits breast cancer cell spheroid proliferation and invasion

Frontiers in Cell and Developmental Biology, Journal Year: 2023, Volume and Issue: 11

Published: Dec. 6, 2023

Breast cancer is characterized by physical changes that occur in the tumor microenvironment throughout growth and metastasis of tumors. Extracellular matrix stiffness increases as tumors develop spread, with stiffer environments thought to correlate poorer disease prognosis. Changes extracellular other characteristics are sensed integrins which integrate these cues intracellular signaling, resulting modulation proliferation invasion. However, co-ordination mechano-sensitive signaling functional groups cells within 3-dimensional remains poorly understood. Here we provide evidence increasing collagen scaffolds results increased activation ERK1/2 YAP human breast cell spheroids. We also show acts upstream this context. further demonstrate YAP, metalloproteinases actomyosin contractility required for remodeling, invasion lower scaffolds. proteins higher gels correlated reduced Our data collectively induce mechano-signaling but contrary from 2-dimensional studies, not sufficient promote pro-tumorigenic effects

Language: Английский

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cDC2 plasticity and acquisition of a DC3‐like phenotype mediated by IL‐6 and PGE2 in a patient‐derived colorectal cancer organoids model

European Journal of Immunology, Journal Year: 2024, Volume and Issue: 54(6)

Published: March 21, 2024

Abstract Metastatic colorectal cancer (CRC) is highly resistant to therapy and prone recur. The tumor‐induced local systemic immunosuppression allows cells evade immunosurveillance, facilitating their proliferation dissemination. Dendritic (DCs) are required for the detection, processing, presentation of tumor antigens, subsequently activation antigen‐specific T orchestrate an effective antitumor response. Notably, successful tumors have evolved mechanisms disrupt impair DC functions, underlining key role dysfunction in promoting growth, metastasis initiation, treatment resistance. Conventional type 2 (cDC2) prevalent been shown present high phenotypic functional plasticity response tumor‐released environmental cues. This reverberates on both development responses efficacy immunotherapies patients. Uncovering processes, mechanisms, mediators by which CRC shapes disrupts cDC2 functions crucial restoring full potential. In this study, we use our recently developed 3D DC‐tumor co‐culture system investigate how patient‐derived primary metastatic organoids modulate phenotype function. We first demonstrate that collagen‐based displays extensive interaction between organoids. Interestingly, show tumor‐corrupted shift toward a CD14+ population with defective expression maturation markers, intermediate positioned monocytes, impaired T‐cell activating abilities. aligns newly defined DC3 (CD14 + CD1c CD163 ) subset. Remarkably, comparable was found be lesions enriched peripheral blood Moreover, using EP2 EP4 receptor antagonists anti‐IL‐6 neutralizing antibody, determined observed partially mediated PGE2 IL‐6. Importantly, holds promise as platform testing therapies aimed at preventing or mitigating dysfunction. Overall, study offers novel relevant insights into (dys)function hold relevance design therapeutic approaches.

Language: Английский

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Tumor-derived colorectal cancer organoids induce a unique Treg cell population by directing CD4+ T-cell differentiation.

iScience, Journal Year: 2025, Volume and Issue: 28(2), P. 111827 - 111827

Published: Jan. 18, 2025

In colorectal cancer (CRC), increased numbers of tumor-infiltrating CD4+ regulatory T (Treg) cells correlate with tumor development, immunotherapy failure, and poor prognosis. To assess how CRC tumors directly modulate Treg cell differentiation, we developed an in vitro co-culture system using from Foxp3eGFP mice tumor-derived organoids. Co-culture resulted a significant increase numbers. RNA-sequencing identified distinct transcriptional profile organoid-induced cells, upregulation genes associated vivo. High expression upregulated correlates shorter progression-free intervals overall survival patients. Human organoids similarly induced enhanced suppressive capacity linked to This model provides insights into differentiation can identify approaches disrupt stimulate anti-tumor immunity.

Language: Английский

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Unveiling the orchestration of T-cell dynamics: A comprehensive examination of their crucial role in revolutionizing immunotherapy for pancreatic and colon cancers

Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown, P. 199 - 232

Published: Jan. 1, 2025

Language: Английский

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Tumor organoids in cancer medicine: from model systems to natural compound screening

Pharmaceutical Biology, Journal Year: 2025, Volume and Issue: 63(1), P. 89 - 109

Published: Feb. 1, 2025

The advent of tissue engineering and biomedical techniques has significantly advanced the development three-dimensional (3D) cell culture systems, particularly tumor organoids. These self-assembled 3D clusters closely replicate histopathological, genetic, phenotypic characteristics primary tissues, making them invaluable tools in cancer research drug screening. This review addresses challenges developing vitro models that accurately reflect heterogeneity explores application organoids research, with a specific focus on screening natural products for antitumor therapies. synthesizes information from major databases, including Chemical Abstracts, Medicinal Aromatic Plants ScienceDirect, Google Scholar, Scopus, PubMed Springer Link. Publications were selected without date restrictions, using terms such as 'organoid', 'natural product', 'pharmacological', 'extract', 'nanomaterial' 'traditional uses'. Articles related to agriculture, ecology, synthetic work or published languages other than English excluded. identifies key efficiency variability organoid generation discusses ongoing efforts enhance their predictive capabilities personalized medicine. Recent studies utilizing patient-derived compound are highlighted, demonstrating potential these new classes anticancer agents. integration presents promising approach discovering novel compounds elucidating mechanisms action.

Language: Английский

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